Landscape of genetic alterations in patients with metastatic uveal melanoma.

9043 Background: Uveal melanoma (UM) is a rare type of cancer with a mutational profile distinct from skin melanoma and poor prognosis in a metastatic setting. In the context of a dose-escalation clinical trial of the PKC inhibitor AEB071 (sotrastaurin) in UM we conducted genomic profiling of 52 formalin-fixed, paraffin-embedded biopsies from metastatic patients (pts), primarily from liver. Methods: Massively parallel sequencing of 288 clinically-relevant cancer genes was performed by Foundation Medicine at high depth (median 646X) to characterize mutations, amplifications (≥6 copies) and homozygous deletions. Results: Alterations of known or likely functional significance were frequent only in genes previously implicated in UM but two novel patterns were observed. All but two pts (96%) had a known activating mutation in either GNAQ (63%; Q209P/L/R or R183Q) or GNA11 (33%; Q209L). While this mutually exclusive pattern is a known feature of UM the higher prevalence reported here is likely due to the sequen...